• Thursday, 16 May 2019 •
Alexandru Trestioreanu (1922-1988), promoter of Romanian surgical oncology and of Romanian oncology school
G.D. Subţirelu, Sînziana Ionescu, V.M. Prunoiu, Octavia Madge, A.M. Marincaş, C. Daha, E. Brătucu
Surgical Oncology I Clinic, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
The aim of this paper is to present the contribution of Professor Alexandru Trestioreanu in promoting and inovating the Romanian surgical oncology, as well as in modernising the oncological therapies in our country, all these being realized in the same time with a large development of the clinical oncology school. The materials and the method used were represented by biographical sources and articles on topics of surgical oncology published during his life by him and his team of collaborators, and also by different chapters on oncology manuals which he contributed to. Among the results of our study, we mention: the contribution to the realisation of a first classification of malignant tumors in our country, as well as advocating for therapeutic associations (multimodal treatment) in order to optimize the results, and also the organisation of a uniform system for reporting neoplasias, through the National Cancer Registry. Among the surgical contributions, we mention the improvement of techniques for some cancers: pelvic exenterations in cervical cancer, lymphadenocolpohisterectomy, laterocervical lymphadenectomy for head and neck cancers, as well as describing a variant of radical mastectomy. The conclusions of this study are represented by the wide inovation activity of the Romanian surgical oncology, with important professional achievements in the field of cervical neoplasia. The personality and the knowledge dissemination of Professor Trestioreanu marked the educational process and the formation of many generations of Romanian surgical oncologists and cancer physicians.
Lung cancer
Non-metastatic pulmonary nodules in oncologic patients
Mihnea Davidescu, Alin Burlacu, Natalia Motaş, Bluoss Corina, Ovidiu Rus, Elena Jianu, Bogdan Tănase, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Pulmonary metastases result from seeding of cancerous cells originating in the primary tumor in the lung. Nearly 30% of cancer patients develop pulmonary metastases in the course of their disease. After the liver, the lung is the secondary most frequent target organ for metastasis in gastrointestinal cancers. Nearly any cancer can spread to the lungs. Patients with a known malignancy undergo multiple follow-up imagistic studies to pinpoint the occurrence of pulmonary metastases, which will allow the initiation of specific treatment regimens. A significant percentage of the lesions found at the control examinations are, in fact, not metastases, but other type of lesions. With this in mind, it is obviously necessary to obtain a histological diagnosis prior to resumption or initiation of the oncologic treatment. We present our experience with over 100 neoplastic patients operated for the confirmation of pulmonary metastases from which 16% were proved to have other types of lesions.
Early stage non-small cell lung cancer (NSCLC) resected non-anatomically – variants of therapeutic management
Natalia Motaş, Mihnea Davidescu, Corina Bluoss, Ovidiu Rus, Veronica Manolache, Mădălina Iliescu, Vlad Alexe, Maria Lungu,David Achim, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
In thoracic surgery worldwide there are cases with known extrapulmonary cancer, oncologically controlled, in which a pulmonary nodule appears. In some of those cases, the clinical judgement leads to non-anatomical lung resection; the frozen section from the nodule may be not conclusive for the primary or secondary cause of lung cancer. After immunohistochemistry, the final diagnosis is non-small cell lung cancer (NSCLC). The postoperative therapy in those cases is not standardized; there are to be considered multiple factors. We present the possible variants and practical situations resolved in our clinic.
Uniportal video-assisted thoracic surgery (uni-VATS) in IOB – extended indications
Natalia Motaş, Veronica Manolache, Ovidiu Rus, Mihnea Davidescu, Mădălina Iliescu, Vlad Alexe, Maria Lungu, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Video-assisted thoracic surgery (VATS) is the natural evolution of the minimally invasive thoracic surgery. The main advantages of VATS are: shorter recovery, less postoperative pain and more rapid initiation of the oncological treatment. In the “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest (IOB), we are performing VATS for lung cancer, lung metastasis, mediastinal masses and esophageal benign tumors.
Video-assisted thoracic surgery (VATS) – a modern approach for lung cancer resection
Bogdan Tănase, Alin Burlacu, Natalia Motaş, Mihnea Davidescu, Corina Bluoss, Ovidiu Rus, Elena Jianu, Violeta Deaconescu, Maria Lungu, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Video-assisted thoracic surgery is a modern treatment approach for benign or malignant pulmonary lesions. In our presentation, we would like to present a review of the literature regarding the quality of the oncological VATS resection and an audit of our VATS experience. The benefits of VATS refer to: reduced thoracic pain after surgery, reduced length of hospitalization, rapid social and economic reintegration, quick recovery after surgery and the possibility of rapid onset of the adjuvant chemotherapy. In this communication we also discuss about the oncological aspect of VATS compared with open surgery – lymph node dissection or sampling, trocar port or pleural seeding problem, possibility of the detection of other intrapulmonary nodules. Overall, we sustain that video-assisted thoracic surgery involves lower morbidity and at least the same oncological results as open surgery.
Pleural thymoma metastases involving lung, diaphragm and liver – case report
Bogdan Tănase, Alin Burlacu, David Achim, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Metastatic malignant thymoma is generally amenable to chemotherapy, but can be surgically treated in selected cases. We present a case of malignant thymoma with indolent evolution: diagnosed in 2011 – biopsy – chemoradiotherapy, operated in 2012 for PET-positive mediastinal mass, reoperated in 2014 for right pleural mass, and presented in our service with a single mass involving RLL, diaphragm and S6 and S7 hepatic segments. Considering the slow growth of the tumor, we decided for surgical resection follow by oncological treatment. We approached the lesion via a thoraco-abdominal incision, and we performed non-anatomic RLL resection en bloc with the resection of the right hemidiaphragm and the S6 and S7 segments of the liver with simple evolution. Malignant lesions involving the diaphragm require complex operative approach; a good view can be obtained by thoraco-abdominal incision for complex hepatic resection.
Surgical approaches in chronic empyema after left pneumectomy for NSCLC
Mădălina Iliescu, Mihnea Davidescu, Veronica Manolache, Corina Bluoss, Natalia Motaş, Ovidiu Rus, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Post-pneumectomy empyema is an uncommon complication, but with high morbidity and mortality in all patients, especially in those undergoing chemotherapy for lung cancer. In the era of antibiotics and minimally invasive treatments, we found ourselves in the position to return to old therapeutic methods. In this article, the authors present the case of a 68-year-old patient who underwent left pneumectomy for NSCLC, with current chemotherapy treatment, who found himself struggling with chronic empyema in the residual thoracic cavity. After several attempts of closed thoracic drainage with no results, we performed an open window thoracostomy to provide a durable method of draining the pleural space. The postoperative evolution was favorable, with no complications; furthermore, we managed to achieve local control of the infection and the patient could continue his chemotherapy.
Management of pleural effusion in oncological patients
Alin Burlacu, Bogdan Tănase, Natalia Motaş, Mihnea Davidescu, Corina Bluoss, Violeta Deaconescu, Maria Lungu, Veronica Manolache, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
In our institute, there are many patients presenting pleural effusion. In this paper we would like to discuss the management of malignant pleural effusion – a review of the literature compared with data from our clinic. Malignant pleural effusion may be secondary to primary or metastatic lung or pleural cancer or extrathoracic malignancies. There are some unanswered questions about the management of malignant pleural effusion: is patient age important, is quality of life important, is disease prognostic the same for all patients with malignant pleural effusion, what is the perfect treatment for each patient? In this communication we would like to discuss about those problems involving malignant pleural effusion with the participation of medical oncologist, radiotherapist and thoracic surgeon. At the end of this presentation we should be able to create some “local guidelines” for the management of these patients.
Tumoral lung entrapment – what can we do?
Vlad Alexe, Natalia Motaş, Veronica Manolache, Maria Lungu, Mădălina Iliescu, Elena Jianu, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
We present the case of a 62-year-old patient diagnosed with massive pleural serohematic effusion of unspecified etiology, hospitalized in our clinic for diagnosis and specialized treatment. Thoracentesis is performed at admission, with approximately 900 ml of serohematic fluid being drained, the procedure ending because of the lack of evacuation pressure. The tomographic examination describes a quasi-circumferential encapsulated massive pleural effusion, which associates iodophilic irregular and pseudonodular pleural thickening suspected to be tumoral, with middle lobe and posterior-laterobazal atelectasis. Based on the clinical and imagistic aspect, it is suspected to be diffuse malignant pleural mesothelioma. Proceeding with right thoracoscopy, we discovered intraoperatively a pachypleura of apparent tumoral nature lining the entire visible area: on the diaphragm, the walls, continuing on the base of the lung, which is tightly adherent circumferentially. After the evacuation of the present fluid in the amount of 2200 ml and the parietal pleura biopsies, it is noted that there is an absence of pulmonary reexpansion and diaphragm ascension, both being blocked by the presence of the thick tumoral pleura. The postoperative evolution is initially favorable, but with persistent right hydropneumothorax due to the remaining pleural cavity, present at discharge. The histopathological diagnosis is revealed to be of lung adenocarcinoma pleural metastases. This case is aimed at highlighting the difficulty of the surgical management of a patient with malignant tumoral lung entrapment.
Early diagnosis of microcellular bronchopulmonary cancer by alternative method of NSE analysis and testing
Claudiu Eduard Nistor1, Raluca-Ioana Ştefan-van Staden2, Camelia Stanciu-Găvan3, Adrian Vasile Dumitru3
1. Thoracic Surgery Department, “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest; 2. National Institute of Electrochemistry and Condensed Material, PATLAB Bucharest; 3. Bucharest Emergency University Hospital
Introduction. Lung cancer ranks first in cancer deaths in the world. Neuronal Specific Enolase (NSE) is a tumor marker characteristic of small cell bronchial carcinoma, being considered an analyte of first choice in monitoring. There is a good correlation between the NSE level, the clinical stage and the extent of the disease. In this context, it is necessary to implement new techniques for rapid analysis with early diagnosis purpose. Experimental sensors. Stochastic sensors based on maltodextrins with dextrose equivalent were used for this type of analyte. The technique is highly sensitive, reliable and reproducible. Stochastic sensors were used for neuron-specific enolase analysis in blood and tumor tissue samples. The tumor tissue sample was processed by conventional and immunohistochemical histopathological methods for the detection of NSE. Results and discussion. Following these treatments, a good correlation was found between the results obtained by electrochemical analysis of NSE in the blood and lung tumor. This technique can be applied for the early detection of microcellular bronchopulmonary cancer. Conclusions. The data show that the applied method may be a valid option for biological sample analysis that provides sufficient results in early diagnosis of microcellular lung cancer. Also, serum levels of NSE could be a benchmark for monitoring the therapeutic response and patient’s evolution. The study aims to increase the life expectancy of patients with microcellular lung cancer.
Recognition. Authors thank UEFISCDI, PN II 22/2014 for financial support.
Immunotherapy with PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC)
M. Albu1, A. Grigorescu2
1. “Victor Babeş” Diagnostic and Treatment Center, Bucharest; 2. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Lung cancer, particularly the non-small cell lung cancer (NSCLC), with its subtypes, represents a global major health issue due to its high mortality. As a result of researchers’ efforts to understand the molecular biology of this particular type of cancer, new therapies have emerged, including immunotherapy. In this short review, we first present recent data about disease-specific epidemiology and discuss the main studies that led to the approval and incorporation of immunotherapy in the first- and second-line therapy of advanced NSCLC in clinical practice. We present the main combinations of systemic therapy and radiotherapy in which immunotherapy is included, also adressing phase II and phase III studies challenging upfront neoadjuvat immunotherapy and its combinations with radiotherapy and conventional chemotherapy. The conclusion is that immunotherapy has brought an important change in the therapeutic paradigm of NSCLC.
Somatostatin analog therapy in metastatic large cell neuroendocrine carcinoma of the lung – case report
Silvana Adelina Gheorghe1, Alina Luminiţa Boldilcu1, Andreea Mihaela Stoica1, Isabela Andra Komporaly1, Bogdan Georgescu1, Raluca Ioana Mihailă1, Dana Lucia Stănculeanu1,2
1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest; 2. “Carol Davila” University of Medicine and Pharmacy, Bucharest
Introduction. Due to the overexpression of somatostatin receptors in neuroendocrine tumors, the treatment with somatostatin analogs (SSAs) has been proven to inhibit tumor growth in patients with unresectable metastatic disease. We present the clinical case of a patient diagnosed with advanced large cell neuroendocrine carcinoma of the lung (L-LCNEC), who received radio-chemotherapy treatment with little benefit. Since the therapeutic shifting on SSA, there was a significant response and an improvement in the quality of life. Case presentation. In October 2016, a 59-year-old smoker female presented at the primary care physician accusing dyspnea and wheezing. A computed tomography (CT) scan was performed, which showed a massive right laterocervical and supraclavicular adenopathic block, with upper mediastinal compression syndrome. She was diagnosed through a lymph node excisional biopsy with L-LCNEC stage IV (M1LYM), poorly differentiated, highly proliferative. One month later, the patient started radiotherapy (total dose of 20 Gy), targeting the mediastinal and cervical adenopathies. Afterwards, she was redirected to our department, at the “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology. Following the complete clinical and paraclinical evaluation (including endocrine biomarkers), the tumor board decided to apply a palliative chemotherapy with etoposid+cisplatin (six cycles). After the treatment, the clinical outcome was good and the CT examination performed in February 2017 revealed complete regression of the laterocervical adenopathies and partial regression of supraclavicular and mediastinal ones. However, in May 2017, the patient accused night sweats and palpitations, the laboratory results showing elevation of the endocrine biomarkers. The therapeutic conduct established the treatment with SSA (Lanreotide Autogel®, 120 mg/month), starting from June 2017. Discussion and conclusions. The subsequent follow-ups revealed a partial response to the oncologic treatment, the patient being stable, without clinical symptoms, with normal biomarkers and no radiologic progression. The last Positron Emission Tomography-CT scan performed showed low metabolic activity in the residual lesions from the lung and mediastinal lymph nodes. The treatment with lanreotide is still ongoing, demonstrating that using SSAs is a valid alternative to chemotherapy in patients with advanced L-LCNEC.
Gastrointestinal cancer
The simultaneous approach of recto-colic and liver resections in stage IV colorectal cancer – oral presentation
Ciprian Cirimbei1,2, Vlad Rotaru1, Simona Cirimbei1,2, Elena Chiţoran1, E. Brătucu1,2, Carmen Pantiş1, Sorela Rădoi1, Monica Olaru1, Adriana Bene1
1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest; 2. “Carol Davila” University of Medicine and Pharmacy, Bucharest
The management of colorectal cancer with liver metastases (CRCLM) is the current topic of discussion, regarding the timing, indications and complications of the three strategies: the classic staging approach (primary tumor resection – hepatectomy 2-3 months after chemotherapy), simultaneous resection – rectal and hepatic, and reversal staging approach (initial hepatectomy – subsequent resection of the primary tumor). Objectives. We propose the retrospective evaluation of the synchronous approach, applied to CRCLM, focusing on the surgical technique, indications, and perioperative complications. Method. Between August 2015 and May 2017, seven patients with CRCLM benefited from simultaneous approach of colorectal and hepatic cancer, and performed rectal resection/colectomy concurrent with hepatic wedge resection associated with radioablation. The monitoring was performed by CT and PET-CT at 3-6 months intervals. The therapeutic algorithm included three pillars: preoperative radiotherapy in rectal cancers (five sessions/5 Gray protocol), 10-day surgery, FOLFOX adjuvant chemotherapy (5-fluorouracil, leucovorin, oxaliplatin) and bevacizumab; colon cancer benefited from the last two therapeutic pillars. Results. In the studied group, two low anterior rectal resections were performed, two rectal abdomino-perineal resection, one right hemicolectomy and two sigmoidectomy; a variable number of metastases ranging between 1-10, with a diameter between 2 and 6 cm, were treated. There were no perioperative complications related to the association of the two procedures, without postoperative morbidity/mortality. At a median follow-up period of 11 months (range: 2-18 months), the death of one patient was recorded by pulmonary thromboembolism, four patients showed no evidence of neoplastic recurrence, two patients had liver metastasis regression, but also signs of peritoneal carcinomatosis; all patients were under the chemotherapy protocol. Conclusions. The experience shows that the simultaneous approach of recto-colic and liver resections in colorectal cancers is a safe procedure, grafted by low morbidity, the limits being dictated by the size of the liver, the distance results being traced through consistent trails.
Video-assisted thoracic surgery (VATS) in digestive surgery: extramucosal esophageal tumorectomy
Natalia Motaş1, Mădălina Iliescu1, Maria Lungu1, Dayana Nechita2, Teodor Horvat1
1. Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest; 2. Department of Anesthesiology, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
We present the case of a male patient diagnosed with a mass situated within the esophageal wall. He is known with an ocular melanoma, resected. We performed extramucosal esophageal complete tumorectomy by uniportal anterior VATS (video-assisted thoracic surgery). We complete the discussions and comments with data from literature.
Surgical importance of anatomic variants of celiac trunk
Elena Chiţoran1, V. Rotaru1, C. Cirimbei1,2, Simona Cirimbei1,2, L. Simion1,2
1. Oncologic Surgery Department I, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest; 2. “Carol Davila” University of Medicine and Pharmacy, Bucharest
Introduction. There is a great number of anatomical differences in the vascular distribution pattern of the celiac trunk and its branches; knowledge of these variants is of great importance in planning a wide array of surgical procedures regarding multiple sites – esophagus, stomach, duodenum, liver, pancreas, biliary tract, spleen. Materials and method. This study aims to perform an analysis of the literature already published on the subject, as well as presenting some case reports from our own experience, cases in which we’ve encountered such anatomical variants and how they influenced our surgical technique. Results. In accordance with the available literature (radiological, clinical and anatomical studies), the typical triple branching of the cealic trunk is encountered in 60-94% of cases. The most common variants of the celiac trunk division are type III and type V Michels, although a significant proportion falls under the unclassified group of the Michels scale (3.9-4.3%). Conclusions. The knowledge of anatomical variants pertaining to vascular structures of the celiac trunk is of capital importance when performing surgery in the superior abdomen due to the need of an appropriate lymphadenectomy, with good oncological response and minimal complications. Performing an angio-CT scan beforehand can reveal such variants, improving the surgical procedure.
Comparative analysis of K-Ras and P53 by electrochemistry and immunohistochemistry in colon cancer
Camelia Stanciu-Găvan1, Raluca Ioana Ştefan van Staden2, Costel Şavlovschi1, Ştefan Neagu1, Adrian Vasile Dumitru1, Narcis Copcă3, Meda Laura Comandaşu1, Radu Petru Adrian4, Claudiu-Eduard Nistor5
1. Bucharest Emergency University Hospital; 2. National Research Institute for Electrochemistry and Condensed Matter, PATLAB, Bucharest; 3. Surgery II Department, “St. Mary” Clinical Hospital, Bucharest; 4. Surgery Department, “Carol Davila” Clinical Nephrology Hospital, Bucharest; 5. Thoracic Surgery Department, “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest
Introduction. Colorectal cancer is the third cause of cancer worldwide mortality. The study aims to find methods for the rapid detection of P53 markers and K-Ras in colon cancer. Comparative testing of blood samples analyzed with stochastic sensors versus immunohistochemical analysis of tumor tissues was performed. The correlation of the results after the use of the techniques mentioned in order to demonstrate the efficiency of the electrochemical analysis was achieved. These genes are responsible for the early development of colorectal cancer. Experimental. The electrochemical analysis for p53 and K-Ras detection used stochastic sensors based on diamond and graphite powders, modified with different types of porphyrins and oleamides. Blood samples revealed high sensitivity at very low concentrations (FG/ml). The immunohistochemical analysis was performed from tumor tissue samples. Results and discussion. Following the P53 and K-Ras determinations by the two techniques, a good correlation of the obtained results was found. The statistical evaluation of the data showed that the blood test with the stochastic sensor is similar to the tissue analysis by immunohistochemistry. Conclusions. The alternative technique has been used for P53 and K-Ras testing in biological samples, as it provides efficient qualitative and quantitative analysis. The data obtained shows that the proposed method can be used as a rapid addition technique for diagnosis or screening in colon cancer, initiating an effective personalized treatment to increase life expectancy among colorectal cancer patients.
Recognitions. The authors thank UEFISCDI, the 22/2014 PNII.
Giant abdominal soft-tissue liposarcoma (case presentation)
Sînziana Ionescu, Dan Subţirelu, Mihnea Alecu, Luminiţa Udrea, Eugen Brătucu, Virgiliu Prunoiu, Marian Marincaş
“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Giant liposarcomas are met predominantly in retroperitoneal localizations. We present the case of a 43-year-old woman, with morbid obesity, suffering from a gigantic tumor with the origin in the subombilical abdominal wall, with an impressive volume and an inferior expansion similar to an “apron” extended to the ankle. This tumoral mass has been developing for five years, according to the patient. The tumor represented a serious problem, drastically limiting the patient’s mobility. The CT scan highlighted the tumor extension to the exterior, as well as the insertion pedicle from the level of the anterior sheath of the right abdominal muscle. Surgical ablation was performed. The histopathological aspects and immunohistochemistry test performed from the tumor’s insertion area established the diagnosis of atypical lipomatous tumor (lipoma-like well differentiated liposarcoma). The subsequent evolution was simple, with the restore of moving mobility and social reinsertion.
Rectal neuroendocrine tumor with an aggressive behaviour
Augustin Marian Marincaş1,2, Virgiliu Mihail Prunoiu1,2, Sînziana Ionescu1, Tudor Marian Proca2, Maria-Manuela Răvaş2
1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest; 2. “Carol Davila” University of Medicine and Pharmacy, Bucharest
Background. Neuroendocrine tumors are rare epithelial neoplasms with specific biologic characteristics which can make the diagnosis and treatment questionable and which, in general, have a good prognosis. Regarding the treatment, tumour dimension is the most important predictor of the tumor behaviour and, even though other characteristics are taken into consideration in order to appreciate the tumour aggressiveness, proliferation index (Ki-67) must be measured, this being the main factor in order to select the option for surgical treatment. Therefore, tumors of less than 1 cm due to the low risk of lymphatic dissemination and distant metastases are recommended for endoscopic excision. For tumors with dimensions between 1 and 2 cm, due to the higher risk of dissemination, there are several discussions involving the surgical treatment. For tumors larger than 2 cm, the treatment is surgical resection with colorectal anastomosis or abdominal perineal resection and loco-regional lymph node dissection. Case presentation. We present the case of a 55-year old Caucasian patient, who addressed for rectal bleeding debuted 6 months previously. At the moment of the hospital admission, the general state of the patient was good, and the clinical and paraclinical exam confirmed the diagnosis of stage IV rectal tumor. The pathology exam could not distinguish between a non-differentiated carcinoma and a neuroendocrine tumour. The diagnosis of rectal neuroendocrine tumor with an aggressive behaviour was established via immunohistochemistry (Ki-67 index of 75-80%, G3 grading). Due to the high aggressiveness of the tumour, the patient had a rapid evolution towards a severe state and the debut of hepatic insufficiency did not allow the systemic anti-tumor treatment. Conclusions. In conclusion, we can say that in the case of rectal neuroendocrine tumors, the stage of the disease and the Ki-67 index have an important prognostic value, and it is crucial for both the diagnosis and tumour aggressiveness to have an immunohistochemistry exam. Even though, in general, they are small well-differentiated tumors with a rather good prognosis, there are forms of tumors with greater dimensions, with metastases and with severe prognosis.
• Friday, 17 May 2019 •
Breast cancer
Possible direction for modifing the axillary lymphadenectomy surgical technique
Vlad Rotaru1, Elena Chiţoran1, Ciprian Cirimbei1,2, Simona Cirimbei1,2, Laurenţiu Simion1,2
1. Oncologic Surgery I Department, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest; 2. “Carol Davila” University of Medicine and Pharmacy, Bucharest
Introduction. The dissection of axillary lymph nodes is a current practice in managing multiple neoplastic diseases for both staging and therapeutic purposes. The current study corroborates data regarding the anatomy of the intercosto-brachial nerve (ICBN) and the benefits of its preservation during complete axillary lymphadenectomy performed as treatment for pacients with breast cancer. Method. The study group consisted of subjects who underwent axillary lymphadenectomy in our clinic between 2014 and 2017; the subjects were randomized into two groups, depending on the type of surgery performed, axillary lymphadenectomy with or without preservation of the sensory nerves. The evaluation consisted of anatomical variants of the ICBN according to the Cunnick classification, cutaneous sensory deficit, pain, number of lymph nodes removed, operating time, complications arisen during and after surgery, and local recurrence rate. Results. Immediate and long-term follow-up of patients have shown a superior tactile sensitivity, reduction or even disappearance of paresthesia and chronic post-surgical pain in the group where ICBN and other sensitive nerves were preserved, as opposed to the one where they were not. There were no significant differences in the number of lymph nodes removed and local recurrence rate in a two-year interval between the two groups, with only a minimal increase in operating time. Conclusions. Preserving the ICBN and other sensory nerves during axillary lymphadenectomy improves the operating technique; it does not affect the oncological result and leads to less pain and sensory disturbances after surgery, with an improvement in the overall quality of life. Considering the evolution of surgical techniques addressed to breast cancer with the resurgence of more and more less invasive techniques, we consider that the axillary lymphadenectomy should follow the same direction and, also, the preservation of sensory nerves during this procedure in an optimal way.
Role of factors with reduced penetrance in invasive ductal carcinoma
Remus Iulian Nica1, Janin Cristian Muşat1, Doriana Vintilescu1, Florina Vasilescu1, Mihai Badea2, Corina Cioban3
1. “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest; 2. Sante Clinic, Bucharest; 3. University of Bucharest
Introduction. The risk factors with reduced penetrance can contribute to the apparition of some malignant diseases or of some endophenotypes. Testing for these risk factors can help in understanding the predisposition to sporadic forms of breast cancer. The aim of this study is to test the impact of risk factors with reduced penetrance in sporadic types of invasive ductal carcinoma in Romanian women. Materials and method. Out of the 672 patients with breast cancer, 69.72% had invasive ductal carcinoma. Consequently, it was realized a case-control study in which there were included 250 women (50-65 years old). They were distributed in the group of patients diagnosed with invasive ductal carcinoma (n=125; average age: 60±3.1 years old) or in the control group (n=130; average age: 58.16±3.75 years old). In the control group there were included women considered clinically healthy, without heredocolateral antecedents of malignant diseases. In each biological sample there were genotyped mutations with reduced penetrance in genes ACE, AGTR1, eNOS, SELL, TGFb and IL6, and the presence of Torque teno viruses (TTVs) using PCR-based methods. MDR analysis (Multifactor Dimensionality Reduction) was used in order to investigate the relations of statistical epistasis between the tested variables. The data were analysed using StatsDirect software. Results. The main non-genetic risk factor associated with breast cancer was the birth of the first baby after the age of 30 years old (p<0.01). The distribution of tested genetic polymorphisms in both groups followed the Hardy-Weinberg equilibrium condition. The disease risk seem to be increased by the association of genetic variants TGFb -509T and IL6-174C, or between ACE D and eNOS b (p<0.01). The TTV frequency was significantly higher in breast cancer patients compared to healthy women (80% vs. 58%; p<0.05). MDR analysis suggested that the interaction between different categories of risk factors (ex.: genetic and non-genetic risk factors) can increase the disease risk. Conclusions. The association between genetic and non-genetic risk factors can increase the risk for invasive ductal carcinoma in the investigated groups or for some endophenotypes.
Importance and utility of biomarkers in mammary neoplasia
Alina Oana Rusu-Moldovan1, Maria Iuliana Gruia1, Florin Radu1, Dan Mihu2
1. ”Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest; 2. Second Clinic of Obstetrics and Gynecology, County Clinical Hospital,“Iuliu Haţiegan” University of Medicine and Pharmacy, Cluj-Napoca
Biomarkers play an essential role in managing patients with invasive mammary carcinoma. For selecting patients who can respond to endocrine therapy, both estrogen receptors (ER) and progesterone receptors (PR) must be measured in all newly diagnosed cases of mammary neoplasia. On the other hand, for selecting the probable response to all forms of anti-HER2 therapy (trastuzumab, pertuzumab, lapatinib or ado-trastuzumab emtansin), determining the HER2 expression or the number of genetic copies is mandatory. The measuring of ER, PR and HER2 must be done both in the primary invasive tumor and in recurrent lesions. Testing for BRCA1/2 mutations is used for assessing the risk in families with high prevalence of breast and ovarian cancer. Ki-67 determination, due to its determined clinical value, to its large disponibility and reduced costs in relation to the available multianalytical signification, can have a prognostic role, especially if the values are decreased or increased. Serum biomarkers such as CA 15-3 or CEA can be used for monitoring therapy in patients with advanced disease who receive systemic therapy. Promising biomarkers which are the object of the assessment include both those with prognostic value and those from the level of circulating tumoral cells. Corroborating these biomarkers has an essential role in treatment personalization, and especially in the follow-up of the neoplastic disease.
Comparative evaluation of HER2 by electrochemical and immunohistochemical determinations in breast cancer
Camelia Stanciu-Găvan1, Sorin Mircea Oprescu1, Raluca Ioana Ştefan van Staden2, Adrian Vasile Dumitru1, Narcis Copcă3, Claudiu-Eduard Nistor4
1. Bucharest Emergency University Hospital; 2. National Research Institute for Electrochemistry and Condensed Matter PATLAB, Bucharest; 3. Surgery II Department, “St. Mary” Clinical Hospital, Bucharest; 4. Thoracic Surgery Department, “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest
Introduction. Breast cancer is the most common malignant tumor diagnosed in women and is the second leading cause of cancer mortality worldwide. This reason is the premise of this study in order to find new and fast methods for the early diagnosis of this disease. The presence of elevated HER2 determinations is associated with poor prognosis. The study tests comparative blood samples analyzed with stochastic sensors versus immunohistochemistry in tumor tissues. Experimental. Stochastic sensors were used to determine HER2 in the blood. Immunohistochemical testing of tissue samples was performed after initial standard histopathological evaluation of tumors required for inclusion in a tumor histotype according to protocols, followed by immunohistochemical tests using four prognostic predictive markers (ER, PR, HER2/neu and Ki67) for framing tumors in a prognostic class based on the St. Galen 2017 consensual criteria. Objectives of the study. Introducing a new method for rapid and safe determination of HER2 for breast cancer; comparative research of blood HER2 determination by electrochemistry and immunohistochemical analysis; correlation of results obtained by electrochemistry and immunohistochemistry; clinical implications of early diagnosis in breast cancer management. Results and discussion. The results achieved showed a good correlation of HER2 through enantioanalysis and immunohistochemistry. The early detection of HER2 can initiate the effectiveness of diagnosis and personalized treatment. Conclusions. Data obtained indicates that the proposed method can be used as a rapid additional technique for the diagnosis or screening in breast cancer, initiating an effective personalized treatment with the aim of increasing life expectancy.
Recognition. The authors thank UEFISCDI, PNII – IDEAS 123/2011.
Statistics on breast cancer in 2018
Iolanda Dumitrescu
“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
The latest international statistical data of the World Health Organization (WHO) issues that breast cancer is the most common cancer in women, with estimated age-standardized (world) incidence rates per 100,000 population in 2018 of 46.3 worldwide, 74.4 in Europe, 54.5 in Central and Eastern Europe and 51.6 in Romania. We considered age-standardized (world) rates as summary measures of the rate of disease that a population would have if it had a standard age structure. Standardization is necessary when comparing populations that differ with respect to age because age has a powerful influence on the risk of dying from cancer. Considering Europe’s regions, Western Europe has an estimated age-standardized (world) incidence rate per 100,000 population of 92.6 (second position), Northern Europe: 90.1 (third position), Southern Europe: 80.3 (fifth position), Central and Eastern Europe: 54.5 (eighth position), as compared with world’s: 46.3 (twelfth position). In Europe, Belgium (113.2), followed by the The Netherlands (105.9) have the highest estimated age-standardized (world) incidence rate per 100,000 population. Regarding the mortality of women, the estimated age-standardized (world) rates per 100,000 population in 2018 were 13 worldwide, 14.9 in Europe, 15.5 in Central and Eastern Europe, and 14.6 in Romania. As estimated age-standardized (world) mortality rate per 100,000 population in both sexes, breast cancer is the second one worldwide, in Europe, in Central and Eastern Europe, and also in Romania, being outstepped by lung cancer. As estimated age-standardized (world) mortality rate per 100,000 population, Western Europe reaches 15.5 (ninth-tenth position), Northern Europe: 14.1 (twelfth position), Southern Europe: 13.3 (seventeenth position), Central and Eastern Europe: 15.5 (ninth-tenth position), and 13 worldwide (eighteenth position). In Europe, Latvia (17.7), closely followed by Ireland (17.6) have the highest estimated age-standardized (world) mortality rate per 100,000 population. Cancer rates have to be kept under control through decreasing prevalence of known risk factors, prevention, early detection, and improved treatment.
Software-aided calcifications detection by local image processing
Iolanda Dumitrescu
“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Introduction. Calcifications are one of the main and earliest indicators of cancer in mammograms. They are present in 50-80% of all mammographically detected cancers, but the pathologic examinations reveal an even greater percentage. Most of the minimal cancers and in situ carcinomas are detected by the presence of calcifications. Aiming to analyze the present situation worldwide, WHO statistics on breast cancer has been issued: in 2018, the estimated age-standardized (world) incidence rate per 100,000 population reached 46.3, and the estimated age-standardized (world) mortality rate per 100,000 population was 13. Method. The technique used is based on local binary patterns, which mean a generalized gray-scale and rotation invariant operator that allows detecting the “uniform” patterns for any quantization of the angular space and for any spatial resolution. If only rotation invariant texture analysis is desired – i.e., gray-scale invariance is not required –, the performance of the operator derived can be further enhanced by combining it with a rotation invariant variance measure that characterizes the contrast of local image texture. Results. The tests have been done by considering mammograms containing calcifications, obtained from the Digital Database of Screening Mammograms (DDSM) (University of South Florida, USA). Conclusion. The technique based on local binary patterns and rotation invariant local variance presents two main advantages: it is very robust in terms of gray-scale variations, and has computational simplicity. The detection of microcalcifications is a very challenging task for radiologists, as well as for computer-aided detection software. Computerized detection of calcifications can be used by radiologists as a “second opinion” and thereby reduces the chances that a cancer is missed. Automated analysis of breast images is the most active area in computer-aided diagnosis research. Further tests are aimed to be done together with clinicians.
Software-aided calcifications detection by signal processing
Iolanda Dumitrescu
“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Introduction. In mammograms, calcifications are seen as bright dots of different sizes. Calcifications are generally very small and they may be missed in dense breast tissue. Another issue is that they sometimes have low contrast to the background and can be misinterpreted as noise in the inhomogeneous background. The exact position of microcalcifications cannot be predicted, as well as their number. By considering each of the European regions and Europe as a whole, the present WHO statistics on breast cancer are issued. In 2018, in Europe, the estimated age-standardized (world) incidence rate per 100,000 population reached 74.4, and the estimated age-standardized (world) mortality rate per 100,000 population was 14.9. Considering Europe’s regions, Western Europe (92.6) has the largest age-standardized (world) incidence rate per 100,000 population. As age-standardized (world) mortality rate per 100,000 population, Western Europe and Central and Eastern Europe both have reached 15.5, being on the first place among the European regions. Method. The technique implemented is based on an algorithm that creates an image in which calcifications are enhanced for easier identification and detection. This is done by subtracting a signal-suppressed image from a signal-enhanced image. Calcifications are segmented in the difference image by thresholding, false calcifications are removed, size and gradient properties are computed. Results. Mammograms containing calcifications, obtained from the Digital Database of Screening Mammograms (DDSM) (University of South Florida, USA), have been used for tests. Conclusion. Calcifications are small densities that appear as bright spots on mammograms, so calcifications detection is generally regarded as a much easier problem than the detection of masses as a result of their more specific appearance. Their visual detection may be difficult without computer-aided detection techniques. Computer-Aided Detection systems play the role of a virtual “second reader” by highlighting suspicious areas for further review and evaluation by the human observer.
Software-aided calcifications detection by time-scale analysis
Iolanda Dumitrescu
“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Introduction. Nearly all breast cancers have an intraductal origin and as long as a cancer remains inside the ductal system, mammography may only reveal it by the presence of calcifications. Calcifications are deposits of calcium inside the breast tissue. A number of calcifications grouped together are termed a cluster, and may be a strong indication of cancer. According to the Breast Imaging Reporting and Data System (BI-RADS) Atlas of the American College of Radiology (ACR), calcifications can be described by their size, morphology and distribution. WHO statistics on breast cancer in Romania in 2018 have been analyzed: the estimated age-standardized (world) incidence rate per 100,000 population reached 51.6 and the estimated age-standardized (world) mortality rate per 100,000 population was 14.6. Method. Time-scale sub-band image decomposition is used to detect and isolate calcifications from the surrounding tissue. Since calcifications are rather small objects, they correspond to the high-frequency components. Standard dyadic wavelet decomposition filters the original image to the desired level, producing sub-images. These ones can contain combinations of low-pass and high-pass components. After suppressing the low-frequency components at the desired decomposition level, the image is reconstructed. Results. The final image has been compared with the quality of the original image. The experiments proved that low-level band elimination (high-pass filtering) in the horizontal, vertical and diagonal details coefficients of the time-scale decomposition led to calcifications with sharper borders in the reconstructed images. Conclusions. Applying the technique using many parameters, differences lay in different decomposition and detection processes, but also in the most important step, and that is the reduction of false positive (FP) results. They can occur often during the calcifications detection process because detection threshold should be set rather sensitive in order to detect as many high-frequency objects as possible, since calcifications can be scattered in the breast tissue.
Urogenital cancer 1
Updates in the management of endometrial cancer
Silviu Cristian Voinea, Angela Şandru, Lăcrămioara Borangic, Cristian Bordea, Alexandru Blidaru
”Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Endometrial carcinoma is the most common female pelvic malignancy in many countries, but not in Romania, where the cervix carcinoma is more common than endometrial cancer. Surgery is the main method for treatment. Unfortunately, it doesn’t exist a gold standard for surgical practice:
extrafascial hysterectomy or radical hysterectomy
extended lymphadenectomy or sentinel lymph node biopsy
open or minimally invasive surgery.
Up to 30% of patients have no risk for lymph node invasion and these patients have no indication for lymphadenectomy:
stage I endometrial carcinoma
no other synchronous cancers
no myometrial invasion
or
myometrial invasion <50%
T≤2 cm
G1/G2.
Lymphadenectomy has an important prognostic role and a questionable therapeutic role. The possible role of sentinel node dissection in endometrial carcinoma patients is to avoid full lymphadenectomy and its related morbidity. The technique is promising and is gaining more credibility. It is crucial to stratify patients on the basis of known clinical and histopathological characteristics, for indication of adjuvant treatment. The novelty (December 2015) is a new risk group: intermediate-high risk, including endometrial carcinoma stage I, G3<50%, myometrial invasion, with or without lymphovascular invasion or G1/G2, regardless myometrial invasion with lymphovascular invasion. Minimally invasive surgery is associated with less morbidity and better quality of life compared with standard laparotomy and is safe even in case of extremely obese patients. The extension of lymphadenectomy remains questionable: pelvic or/and paraaortic lymphadenectomy, the right number of excised lymph nodes, the indication and extension of paraaortic lymphadenectomy. The surgical staging remains the most important surgical procedure, being determinant for prognosis and for indication of adjuvant treatment. Nowadays, the surgical staging is the first step for endometrial cancer and the indication for neoadjuvant treatments is very rare and usually applied only in advanced stages.
Cytoreductive surgery in advanced ovarian cancer: is it worth the effort?
V. Prunoiu, M. Marincaş, T. Proca, Maria Ravaş, E. Brătucu
First Clinic of General Surgery and Surgical Oncology, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Introduction. Surgery remains essential in the treatment of advanced ovarian cancer and the purpose of surgical cytoreduction is to remove the maximum possible of the tumour and its metastases, so that the residual neoplastic mass is ≤1 cm. In this way, both the efficacy of chemotherapy and patient survival are increased. Materials and method. We made a four-year retrospective study on the patients from the First Clinic of General Surgery and Surgical Oncology, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, in which we monitored 105 patients with stages III and IV of ovarian cancer. In 50 patients, we also performed (apart from hysterectomy, bilateral adnexectomy and omentectomy) multiple visceral resections, such as: enterectomy, segmental colectomy, appendectomy, cystectomy, radiofrequency ablation, metastasectomy, abdominal wall resection, pelvic lymphadenectomy and interaortico-caval lymphadenectomy. Results. Although these patients presented in advanced stages of disease, with short life expectancy, primary cytoreductive surgery –sometimes even secondary (or tertiary), all in association with adequate chemotherapy – allowed the increase in quality of life and in survival with 13 months for suboptimal surgery and with 30 months for optimal surgery. Conclusions. Extensive cytoreductive surgery in advanced ovarian cancer is justified by the increase in patient survival and we consider that it should be practiced in specialized units, and that the collaboration between surgeon and oncologist is essential in order to obtain the best results.
Sufficient therapeutic conduct in low-grade ovarian cancers versus absolutely necessary therapeutic conduct in high-grade ovarian cancers (preliminary results)
G.D. Subţirelu, A.M. Marincaş, C. Daha, V.M. Prunoiu, Sînziana Ionescu, E. Brătucu
Surgical Oncology I Clinic, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
The aim of this research is the assessment of the treatments realized and of the results obtained in the context of a great variety of ovarian epithelial cancers, which were grouped in low-grade (LG) (borderline tumors and G1), and high-grade (HG) (G2 and G3 tumors). Materials and method. This is a retrospective study that evaluated the data of 350 patients diagnosed with epithelial ovarian cancers, operated between 1.01.2012 and 31.12.2018 in the Surgical Oncology I Clinic, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, of which 91 were LG and 240 were HG; 19 cases couldn’t be evaluated. Results. The patients with low-grade ovarian neoplasias had interventions such as total histerectomy with bilateral anexectomy, while omentectomy was associated in 77 patients, and four patients had multiorgan resections. Adjuvant/neoadjuvant chemotherapy was associated in 18 cases. In patients with high-grade neoplasia, the surgery included an increased number (62) of multivisceral resections. A total number of 210 patients benefited from cytostatic chemotherapy. The conclusions were that high-grade ovarian neoplasias, having more extended lesions and higher aggressivity, necessitated more frequently multiorgan surgery, while low-grade tumors required less often extended surgery, but necessitated lesional inventory and adequate surgical resections in order to prevent the recurrence.
Role of complete clinical examination in neoplasm staging and therapeutic decision
C. Ilie1, V. Rotaru1, Elena Chiţoran1, Simona Cirimbei1,2, Andreea Ilie1, L. Simion1,2, C. Cirimbei1,2
1. Surgical Oncology I Clinic, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest
Purpose. The complete clinical examination of the patient at admission is sometimes definitory in the staging of neoplasms and the decision of the appropriate therapeutic course. Materials and method. We present a clinical case of a 36-year-old female patient, diagnosed with cervical cancer, who performed radiotherapy as first therapeutic step, for which preoperative imaging (thorax-abdomen and pelvis scanner) did not reveal any suggestive tumor formation for secondary determinations, which would have changed the therapeutic decision at that time. At the clinical examination performed prior to the intervention, the presence of a supraclavicular adenopathy with suspicious characteristics is signaled, therefore it was decided to complete the surgical step with excision biopsy of the supraclavicular adenopathy. Results. The histopathological examination revealed massive carcinomatous infiltration in the supraclavicular adenopathy. Under these conditions, after the meeting of the oncology committee, the therapeutic decision was modified by the addition of adjuvant chemotherapy. Conclusions. Although the remote localizations of lymphatic secondary determinations in cervical neoplasia are rare, their diagnosis in preoperative management is necessary to establish an appropriate therapeutic decision. Although the patient followed all the steps of the pre-therapeutic evaluation existing in the current therapeutic guide, the clinical examination was able to detect secondary determinations that were not evidenced by the other paraclinical examinations.
Lung cancer
Immune therapy in stage III NSCLC: do we have a new standard of care?
Mircea Dediu
Sanador Clinical Hospital, Bucharest
Concurrent chemoradiation was consecrated as standard of care for inoperable stage III non-small-cell lung cancer (NSCLC), more that 15 years ago. Ever since, many strategies have been attempted in order to improve the clinical outcome of the patients, but unfortunately none proved to be successful. Recently, the immune therapy tsunami profoundly altered the classical chemotherapy approach in metastatic non-oncogene driven NSCLC. Nowadays, immune therapy represents the preferred option in first line for patients with >50% PD-L1 expression, and for virtually all patients in second line setting. Last year, at ESMO congress, the PACIFIC trial results were presented. PACIFIC used durvalumab, a PD-L1 inhibitor, as consolidative treatment upon concurrent chemoradiation, and was the first trial communicating a substantial improvement in the outcome of stage III NSCLC patients. As a result, the NCCN guidelines included the PACIFIC trial strategy as the only recommended treatment for this patient’s subcategory. This presentation will briefly review the previous failing approaches attempted to improve treatment efficacy in non-operable stage III patients, along with the major advances reported with immune therapy in the PACIFIC trial.
Importance of the intensive care unit for treatment of advanced lung cancer patients
Alexandru C. Grigorescu
Department of Medical Oncology II, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
In our days, the commission of therapeutic indication in cancer is more and more important for prescribing the best treatment for cancer. In this overview, we present the main situation where there is needed the participation of a specialist in intensive care for patients with advanced lung cancer. Many studies on patients selected to intensive care unit (ICU) admission try to assess the long-term mortality, the quality of life, the ability to continue chemotherapy, and the economic cost. Some studies are contradictory, and the admission of patients with stage IV in ICU was considered not beneficial for patients and with high costs. Nevertheless, the tendency of admission in ICU has increased. In this regard, in a study reported in the Journal of Oncology Practice, Mrad et al. found an increase in the proportion of patients with stage IV lung cancer admitted to the intensive care unit during terminal hospitalization between 1998 and 2014. A large increase in palliative care contacts also occurred, although related cost reductions did not make up for increased ICU costs. Other aspect revealed in the medical literature was the fact that patients with poor baseline performance, multiple organ failure, and evidence of disease progression while receiving treatment seemed less likely to benefit from admission to the ICU. An interesting study comes from South Korea. The authors introduced the term “intensivist” care and started the intensive care services dedicated to pulmonology intensivists. After the introduction of the critical care specialist, they admitted patients eligible for intensive care and used a multidisciplinary approach. The study demonstrated that the implementation of the intensivist system reduced hospital mortality, ICU length of stay, and hospitalization period in advanced lung cancer patients.
Urogenital cancer 2
Pelvic exenterations role in the treatment of locally advanced pelvic cancers
Elena Chiţoran1, V. Rotaru1, C. Cirimbei1,2, I. Burlănescu1, C. Daha1,2, L. Simion1,2
1. Oncologic Surgery I Department, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest
Introduction. For a long time omitted from the treatment guidelines for advanced genitourinary and digestive cancers, at present pelvic exenterations have been reintroduced as surgical treatment methods in locoregional advanced cases, sometimes even with radical intent. Materials and method. The present study was conducted at the Bucharest Oncology Institute, Surgical Clinic I, between 2008 and 2014, on a group of 60 patients with pelvic exenterations, monitoring mortality, morbidity and survival rates. Results. Analyzing the studied group, we found that a radical intervention was possible in over 70% of cases, and even where radical resection could not be done, pelvic exenteration brought major survival benefits and improvement in quality of life. We also noticed better survival after pelvectomy for low digestive cancers or bladder cancer than for genital neoplasms. Conclusions. Although they cause high morbidity, pelvectomies are associated with low perioperative mortality and improved survival rates, when compared to adjuvant therapy used as the only treatment method.
Immunosuppression as a factor of negative prognosis in curable cervical cancer
Elena Mihaela Vrabie1, Mihnea Alecu1,2, Mihai Vintilă1, Elena Chiţoran2, Vlad Rotaru2, Vladimir Poroch3,4, Laurenţiu Simion1,2
1. “Carol Davila” University of Medicine and Pharmacy, Bucharest
2. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
3. “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi
4. Regional Institute of Oncology, Iaşi
Human papillomavirus (HPV), especially subtypes 16 and 18, plays a major role in the etiology of cervical cancer. HPV infection is controlled through both local and systemic immune responses, immunosuppression influencing the persistence, recurrence and progression of the disease. In curable stages, when the standard intervention (Wertheim procedure), that follows radiotherapy, reveals a sterile biopsy fragment from an oncological standpoint, a favorable turnout is expected for the patient. However, there are situations where the evolution of the disease is in contradiction with the excellent response immediately following the surgical intervention. We are hereby presenting the case of two patients (35 years old and 45 years old, respectively) with cervical cancer in stages IA and IIB, respectively, both of which underwent radiotherapy, followed by lymphadeno-colpo-hysterectomy with ilio-obturatory lymph nodes removal. The histopathology revealed a negative result for cancerous cells. In less than a year, both patients developed massive pelvic cancer recurrence, inoperable, unsuitable for radiotherapy, and rapidly progressing while under chemotherapy. One patient was lost from observation six months later, after resorting to palliative care at home, using a urinary catheter to maintain the urethra permeable. The other underwent chemotherapy, but showed local neoplastic progression. One year after the initial intervention, a tumor occupied the pelvis and caused rectal stenosis. Terminal colostomy in the left flank was performed. Both patients associated causes of immunosuppression: the first was HIV-positive, with undetectable viremia under therapy, and the other was treated with corticosteroids for a rheumatic ailment. Studies show that HIV-positive patients are prone to more frequent HPV infections and cervical dysplasia (as immunosuppression reactivates HPV infection). An impaired local immune response, with decreasing CD4+ lymphocyte numbers, associated with the expression of multiple HPV subtypes and low Langerhans cell numbers directly correlate with the stage of the disease. Iatrogenic immunosuppression in patients with rheumatic illnesses contributes to the persistence and indeed the recurrence of the HPV infection, favoring cancerous processes. These cases show that immunosuppression favors HPV infection, cancerous progression and recurrence. Precocious detection and improvement of the immune functions help reduce recurrence rates and complications.
The impact of indocyanine green on the assessment of sentinel lymph node in early stage gynaecologic cancers during minimally invasive treatment. What is the best alternative: ICG, conventional radiotracer or blue dye?
C.B. Coroleucă1, C.A. Coroleucă1, M. Radu2, D. Comandaşu1, D. Mihai1, E. Brătilă1
1. “Prof. Dr. Panait Sîrbu” Clinical Hospital of Obstetrics and Gynaecology, Bucharest, “Carol Davila” University of Medicine and Pharmacy, Bucharest
2. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, “Carol Davila” University of Medicine and Pharmacy, Bucharest
Objective. The aim of this paper is to present the detection rate of the sentinel lymph node in patients with incipient gynaecological cancers using indocyanine green (ICG) in comparison with technetium-99m and blue dye. Materials and method. We analyzed the detection rate, sensitivity, specificity, negative and positive predictive value of each detection method (indocyanine green, conventional radiotracer and blue dye). The analysis included 21 papers that investigated the use of ICG, conventional radiotracer and blue dye in the detection of sentinel lymph node. Results. Sentinel lymph node mapping using indocyanine green is superior regarding the overall detection rate of sentinel lymph node when compared to conventional radiotracer Tc99m and blue dye. Conclusions. The technique using indocyanine green and near-infrared imaging is a useful tool in the management of patients with incipient gynaecological cancers. The overall detection rate is comparable or superior to other techniques. This technique results in higher detection rates of bilateral lymph nodes which consequently reduces the rate of systemic lymphadenectomies. This aspect translates in a reduction of the duration and costs associated with the treatment of cancer patients.
Anterior pelvectomy – therapeutic solution in locoregional advanced bladder tumor (case presentation)
I. Burlănescu1, V. Rotaru1, Elena Chiţoran1, Simona Cirimbei1,2, C. Ilie1, Andreea Ilie1, C. Cirimbei1,2
1. Surgical Oncology I Clinic, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest
Purpose. At present, it is well considered that bladder or genital tumors with locoregional invasion may benefit from extensive block resections, such as anterior, posterior or total pelvectomy. Materials and method. We present a clinical case of a patient for whom it was practiced anterior pelvectomy with cutaneous ureterostomy for an infiltrative bladder tumor with extension to the right ureter, the anterior uterine and vaginal wall. Results. Considering the continuing evolution of postoperative support methods in ATI departments that allows the execution of increasingly complex interventions, we found that pelvectomy, although it can be grafted by postoperative complications, remains the elective surgery to obtain the radicality surgical treatment of bladder or genital tumors with significant locoregional invasion. Conclusions. In the context of “high-volume” institutions, with anesthesia-surgical teams involved in proper peri- and intraoperative management of neoplasia in the gynecological sphere and the urinary system, the anterior pelvectomy preceded or not by radiotherapy becomes a gold standard therapy and it must be done in all cases, regardless of the multiorgan resections that are necessary to achieve this goal.
Young testicular cancer
Ionuţ Ciprian Iorga, George Panait
Faculty of Medicine, “Ovidius” University of Constanţa, “St. Andrew the Apostle” Emergency County Clinical Hospital, Constanţa
Introduction. Testicular cancer is the most common tumor of the young male aged between 15 and 40 years old, with an increased addressability after the age of 20 years old. If detected early, the chances of survival are high, the evolution being favorable. Most of the time, the patient’s addressability is at a late stage when they present in the urology cabinet for the increase in the volume of the testes. Incidence. Although it is relatively low, the mortality continues to be growing among young people due to complications of secondary determinations. Cases presentation. 1) A young male, 20 years old, with right testicular tumor, the preoperative diagnosis was placed on the brain CT, abdomen and pelvis, which detected multiple metastases with straight, retroperitoneal funicular localization in the form of a mass of 10/8 cm, pulmonary, cerebral lobe straight frontal, in the form of a tumor mass with tumor lysis effect, peritumoural edema and peritumoural haemorrhage, which urgently required radical straight orchidectomy. The histopathological exam confirmed the diagnosis of testicular coriocarcinoma 70% + embryo carcinoma 30%. The evolution was stationary. 2) A young male, 26 years old, with left testicular tumor, presented in ambulatory for left testicular pain, increased volume of the testicle, a palpable left supraclaviculary adenopathy, with dimensions of 4/4 cm. We made the diagnosis on the clinical exam and CT of the abdomen and pelvis that required supplementing with MRI. It was found a seminal left testicular tumor with multiple iliac and pelvic determinations, liver and pulmonary, which is why it was practiced left radical orhidectomy. The anatomopathological exam confirmed the seminomatous tumor, the patient being referred to the oncology service for therapeutic conduct, the evolution being slowly favorable. Conclusions. Testicular cancer remains a continuous challenge for any clinician in front of a modern young man, to which an association of clinical and paraclinical investigations, with appropriate follow-up and treatment, hormonal and ultimately surgical, without which the pathological result is not possible. The treatment of refractory testis cancer remains a significant challenge.
Clinical case of seminoma therapy followed by consequential nephrectomy
for retroperitoneal metastasis after four years
Sorin Bulgariu
“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Seminoma is the most common pure germ cell tumor (GCT) of the testis, accounting for up to 50% of cases. Testicular seminoma is a pathological diagnosis in which only seminomatous elements are observed upon histopathological review after a radical orchiectomy and in which serum alpha-fetoprotein (AFP) is within the reference range. The case described is of a 45-year-old man who underwent a left inguinal orchiectomy for testicular tumor in 2015, followed by two chemotherapy courses (2015 and 2016) with carboplatin. The histopathological appearance was of testicular pT2 seminoma. The histopathologist also recommended an immunohistochemistry examination, which has not been performed. In February 2019, the patient was hospitalized in a urological clinic for common symptoms, but the CT scan revealed the left second-degree ureterohydronephrosis by a lateroaortic mass. In February 2019, a retroperitoneal lymph node dissection has been performed (lateroaortic retroperitoneal tumor, retroaortic, interaorta-cava, incorporating the left renal artery, inferior mesenteric artery and left ureter, with secondary second-degree ureterohydronephrosis), and left nephrectomy was performed as well. Associated vascular pathology also required left adrenalectomy. The histopathological examination of the retroperitoneal tumor found secondary lymph nodes and pyelocaliceal seeds from germ cell tumor seminoma. In April 2019, the patient was hospitalized at the “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, for further investigations and complementary treatment. The particularity of the case is the unexpected and unusual necessity of removing the kidney as a consequence of the secondary seminomal determinations. Interesting but hard to be determined is whether the retroperitoneal tumor was synchronic or metachronic to the testicular tumor.
• Saturday, 18 May 2019 •
Minimally invasive cancer
Transthoracic and intrathoracic splenectomy
Alexandru-Mihail Boţianu, Petre Boţianu, Adrian Dobrică, Alexandra Ioniţă, Martha Kész, Mircea Stoianu, Olivia Batog
Surgery II Clinic, University of Medicine, Pharmacy, Sciences and Technology of Târgu-Mureş
The authors present: 1) transthoracic splenectomy for intrasplenic hematoma associated with left intrapleural organised hematoma, massive posttraumatic suffocating pleuresy and multiple rib fractures caused by falling; 2) intrathoracic splenectomy and five layers phrenoplication (Boţianu’s procedure) for a sectorial posterolateral diaphragmatic hernia with complete intrathoracic adherent intraherniary spleen. The postoperative evolution was good, with healing.
Personal procedure of phrenoplasty-phrenoplication in 5 layers in diaphragmatic relaxations and eventrations treatment
Alexandru-Mihail Boţianu, Petre Boţianu, Adrian Dobrică, Alexandra Ioniţă, Olivia Batog, Martha Kész, Mircea Stoianu, Olivia Batog
Surgery II Clinic, University of Medicine, Pharmacy, Sciences and Technology of Târgu-Mureş
The procedure uses a thoracic approach and consists of an anterior wide phrenotomy (which allows to solve concomitant abdominal lesions), followed by the creation of two diaphragmatic folds in sagittal plane, which are sutured both between them and to the diaphragm. The final result is a reconstruction in 5 layers at the site of maximum mechanical load. Step 1: left low postero-lateral thoracotomy. The diaphragm appears very thin and there are no efficient contractions. Step 2: large anterior phrenotomy, avoiding the phrenic nerve branches damage. Step 3: the placement of horizontal “U” stitches, as distal as possible to obtain a maximum horizontalization of the diaphragm. The abdominal viscera is protected by a soft gauze and the assistant’s hand – if necessary, repair of abdominal lesions – in our patient, an associated gastric volvulus solved by gastropexy (lower right). Step 4: the tightening of horizontal “U” stitches creates two sagittal ridges which are strengthened by another row of “U” stitches. The two sagittal ridges are cross-sutured to each other and the diaphragm. The result is the horizontalization of the diaphragmatic application in 5 layers at the place of maximum mechanical load.
Decision no. 858/15.11.1990, no.135249, licence no. 102500 OSIM, Romania.
Pleuro-pericarditis as first diagnosis of malignancy in a bilateral mammary autoamputation
Veronica Manolache, Natalia Motaş, Ovidiu Rus, Mădălina Iliescu, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Usually, when a patient presents with a tumor, we manage the case always keeping in mind that there is potential for malignancy. Sometimes, after the anatomopathological exams, this is not the case or sometimes we don’t have a confirmation of malignancy of the primary tumor. We present the case of a 54-year-old female patient known with bilateral breast tumors with no histopathological confirmation for malignancy who at presentation had bilateral mammary autoamputation. The patient was admitted to our clinic with bilateral pleurisy and pericarditis. Uniportal right VATS surgery is performed to drain the pleurisy and the pericarditis and for biopsies. Left pleurisy at the moment wasn’t necessary to drain. After surgery the patient recovered well and uneventful. The histopathological exam from the biopsies of the pleura and pericardium concluded a carcinoma. This is an instructive oncology case giving the fact that the patient had bilateral mammary tumors with no confirmation of biopsies and underwent chemotherapy treatment. To our knowledge, there are only three cases cited in literature of mammary autoamputation.
Cervical-mediastinal desmoid tumor – a challenging surgical case
Ovidiu Rus1, Natalia Motaş1, Cristian Voica2, Veronica Manolache1, Mădălina Iliescu1, Teodor Horvat1
1. Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
2. Clinic I of Cardiac Surgery, “C.C. Iliescu” Institute of Cardiovascular Diseases, Bucharest
Desmoid tumors are noncancerous growths that occur in the connective tissue. Usually, these tumors are infiltrative, well differentiated, producing local deformity, and their morbidity and mortality results from the effects on the close proximity vital organs. We present the case of a female patient, M.V., 31 years old, diagnosed with left cervical-mediastinal desmoid tumor through biopsy. The importance of the case consists in locating the tumor and its impact, such as the compression on the vascular structures nearby, and it was done so by assembling a multidisciplinary team of both thoracic and vascular surgeons. The tumor was excised completely without any major impact on the vital organs or vascular structures nearby, and the patient had a favorable and uneventful recovery.
The surgical excision of PET-CT metabolically active lesions – a recent challenge
Codruţ Cosmin Nistor-Ciurba1,2, Doina Piciu1,2, Dan Tudor Eniu1,2, Florin Laurenţiu Ignat1,2, Alin Cristian Rancea2
1. “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca
2. “Prof. Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca
Introduction. The increasing use of PET-CT scans over the last few years in the follow-up of oncologic patients led to the apparition of a new type of surgical intervensions, namely the excision of metabolically active lesions, suspected of being secondary determinations of cancers already under surveillance, which are often multidisciplinary treated, following surgical, chemotherapeutic and/or radiotherapeutic stages, targeted therapies etc. Aim. The paper presents some aspects of the excision of these lesions, sometimes unaparent on CT or MRI, lesions that can be a challenge due to their localization. Materials and method. We used the casuistry of the “Prof. Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca. Personal intraoperative iconography of the first author (with the informed consent of the patiens regarding photos and data used for research and publication). Results and discussion. There were identified intraoperatively the lesions in all cases and excised. All the excised lesions suspected to be secondary determinations metabolically active on PET-CT were confirmed after the pathological examination, regardless of the primary tumor type, the dimension of the lesion and its localization, which shows the excellent specifity of this investigation, despite the small number of available cases yet. The excision of these lesions can be a challenge for surgeon in case of more difficult localizations (unique paraaortic lesions, lesion in the renal sinus etc.). Conclusions. After the age of CT, and of MRI, the surgical oncology entered the age of PET-CT as a method for detecting the lesions highly suspected of being secondary determinations, some of them not being highlighted by CT or MRI.
Surgical options in post-excision defects for head and neck tumors
Andrei Marin1, Georgiana-Gabriela Marin2, Ruxandra Mihai1
1. Plastic Surgery Department, “Bagdasar Arseni” Emergency Hospital, Bucharest
2. Cardiology Department, “Prof. Dr. C.C. Iliescu” Cardiovascular Emergency Institute, Bucharest
Among the most frequent tumors for which the patients present themselves to the doctor are the head and neck tumors. When the facial region is involved, the emotional impact can trigger one in two responses: either a very early presentation, in which the post-excision defects are small and can be sutured primarily, or a very late presentation, when a skin graft or a flap may be necessary for coverage. The tumors in the cephalic extremity may involve structures from different systems and therefore a multidisciplinary approach involving other specialists (ENT, oro-maxillo facial surgery, ophthalmology, dermatology, neurosurgery) is required. The treatment ladder involves the following options: primary suture, per secundam healing, skin graft, tissue expansion, local/regional flaps, free flaps. The facial region has both functional and aesthetic importance. The division of the face in aesthetic units offers a guideline which must be respected when choosing both the technique, as well as the position of the incisions. The functional criteria involve preserving the mimics (complete contention of the eyes, mouth, functional and symmetric smile, microstomia prevention). There are protocols and specific interventions for each region of the face (orbital, nasal, buccal, cheek zone) depending on the localization, type and size of the tumor. The oro-maxillo-facial tumors form a separate type of pathology which can generate severe dysfunctions. These can be more difficult to diagnose and the operations may sometimes have serious complications (salivary fistulas, iatrogenic facial paralysis). To sum up, head and neck tumors require following strict rules for optimal aesthetic and functional results and sometimes multidisciplinary approach may be a solution.
Breast cancer
Neoadjuvant clinical trials in early stage breast cancer: is pathologic complete remission a reliable surrogate marker for overall survival?
Mircea Dediu
Sanador Clinical Hospital, Bucharest
Many analyses on the efficacy of neoadjuvant treatment (NAT) for early breast cancer, including a metaanalysis derived from 10 randomized trials, came to the conclusion that patients who would achieve pathologic complete response (pCR) following NAT would experience significant improvement in disease-free survival and overall survival (OS). Thus, pCR was proposed as a surrogate endpoint for OS, with pCR representing a robust prognostic marker for survival at an individual level. In the current analysis, we argue that OS following NAT-induced pCR might have reflected the start-line prognosis of patients mainly defined – among other factors – by the initial pathological lymph node status while being largely independent on the type of administered treatment, thus pleading against the pCR surrogacy hypothesis. We, therefore, propose to redefine pCR as a surrogate endpoint of NAT trials by the involvement of additional biologic parameters.
Gastric cancer
Managing enteral nutrition complications in oncologic patients
Laurenţiu Simion1,2, Mihnea Alecu1,2, Mihai Vintilă1, Elena Mihaela Vrabie1, Elena Chiţoran2, Vlad Rotaru2, Vladimir Poroch3,4
1. “Carol Davila” University of Medicine and Pharmacy, Bucharest
2. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
3. “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi
4. Regional Institute of Oncology, Iaşi
Oncologic therapy, whether curative or palliative, requires an adequate nutritional intake, so that the patient is able to cope with the neoplastic disease, its complications and any treatment side effects that may occur. When oral nutrition is no longer possible, efficient medium and long-term alternatives are percutaneous endoscopic gastrostomy (PEG) and its variations, such as PEG-like, classical gastrostomy and classical jejunostomy. The preferred variant is the PEG, however, when endoscopic passage is no longer feasible, a PEG-like device with a small balloon is used, installed through the means of a minilaparotomy. Although well tolerated by patients, these devices are not without their complications and need periodic replacement. In our experience of over 5 years of installing such devices, we hereby present incidents, complications, as well as ways of overcoming them and specific care instructions for those patients. Even though the effort of ensuring an adequate nutrition is not by itself an effective way of treating cancer, the role of nutrition is indispensable in both oncologic and palliative care, in improving the overall quality of life for the patients.
Varia
Pathogenesis of the cancer
Valentin Curosu
Medicover Constanţa
Malignant tumor is only the effect of appearance of neocellgenesis inside a tissue of the organism. As long as we do not identify and abolish the cause that induces the appearance of this neocellgenesis, we will vainly destroy – until the last one – all the malignant cells from the organism, because the risk of recurrence remains an imminent one. Cancer is the malignant (or major) form of neoplasia; cancer has a unique pathogenesic mechanism that enriches different clinical forms depending on the tissue at which level appears the malignant neocellgenesis.
Gliosarcoma: an uncommon variant of glioblastoma
Ionela Bîzu1, Maria-Iuliana Gruia2, Rodica Anghel2,3
1. Hospital OncoFort, Bucharest
2. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
3. “Carol Davila” University of Medicine and Pharmacy, Bucharest
Introduction. Gliosarcoma is defined as a glioblastoma variant, according to the 2016 World Health Organization (WHO) classification. It is a biphasic neoplasm, consisting of both gliomatous and sarcomatous components. Materials and method. A 58-year-old woman presented in 2018 to the neurosurgery department with complaints of headache for two weeks. The magnetic resonance imaging (MRI) of the brain showed a heterogeneous mass, measuring 3/3 cm with central necrosis and perilesional edema, seen in right temporo-occipital lobe, and very close to the transverse venous sinus. The partial resection of the tumor was performed. The postoperative histopathology report showed features of gliosarcoma, and immunohistochemistry (IHC) showed glial fibrillary acidic protein (GFAP) focal positivity, in areas of gliomatous differentiation, in contrast with lack of immunoreactivity for GFAP in the sarcomatous component. IHC also showed: Ki-67 proliferative index of the tumor 30%, izocitrate dehydrogenase-1 (IDH-1) negative, and O6-methylguanine DNA methyltransferase (MGMT) negative. The patient performed adjuvant chemo-radiotherapy with temozolomidum 75 mg/m2 followed by six cycles of adjuvant chemotherapy with temozolomidum 150-200 mg/m2 for five days, every four weeks, as per Stupp regimen. To the report’s data, the patient has a stable disease condition and continues with observation. Discussion. Gliosarcoma is an uncommon brain tumor, accounting for 2% of all glioblastoma cases and 0.59-0.76% of all brain tumors. It is most frequently seen in patients aged between 40 and 60 years old. Males are more frequently affected than females, with a sex ratio of 1.8:1. Gliosarcoma occurs commonly in the cerebral hemispheres, involving the temporal, frontal, parietal and occipital lobe, in decreasing frequency. Conclusions. The tumor has a clinical presentation, a natural history and a radiological profile similar to glioblastoma multiforme. The case is presented here for its rarity.
Correlation between induction of apoptosis in B-CLL by various drugs and inhibition
of no production
Viviana Roman, Marinela Bostan
Center of Immunology, “Ştefan S. Nicolau” Institute of Virology, Bucharest
B-cell chronic lymphocytic leukemia (B-CLL) is characterised by defective apoptosis that cannot be explained solely on the basis of the known chromosomal abnormalities. Our group and other have reported that the leukemic cells spontaneously display the inductible isoform of nitric oxide synthase (iNOS). The inhibition of the iNOS pathway leads to increased apoptosis of the tumoral cells in vitro, indicating that the endogenous release of NO contributes to their resistance to the normal apoptotic process. The factors that induce the expression of iNOS in vivo in the leukemic cells are not yet identified. The apoptotic process can be divided into three phases: an induction phase, the nature of wich depends on the specific death-inducing signals, an effector phase, during which the “central executioner” is activated and the cell becomes commited to die, and a degradation phase, during which cell acquire the biochemical and morphological features of end-stage apoptosis. In order to modulate the anti-apoptotic role of NO in B-cell chronic lymphocytic leukemia, we tested different families of biologic active compounds.
The study of Elpida 1 vaccine in hepatomas
Dan Iulian Santa
ELPIDA Research Inc SRL, Bucharest
Hepatoma represents a neoplasia with a rapid evolution, of 6-8 months, with a limited prognosis and with less satisfactory therapeutic possibilities. It is the fifth in the world in terms of frequency and the fourth as mortality. The latest PD-L1/PD-1 therapies, the cytostatic treatment, ozonotherapy, and radiotherapy have little results. The present study uses a vaccine combination consisting of antitumor action microorganisms, respectively, the Reflor Forte probiotics and a component composed of hepatic tumor antigens. The two components are reconstituted into a single vaccine component at the time of admission, strictly subcutaneous. It is an immuno-prophylactic unique vaccine concept consisting of natural, non-adverse microorganisms, with specificity towards the tumor-specific tissue, with low manufacturing costs and not requiring sophisticated equipment. As a mechanism of action, it involves the activation of macrophages and T8 lymphocytes on the classical pathway, by changing the tumor environment, triggering cell death, apoptosis and necrobiosis of tumor cells, with the release of cytokines, chemokines, interferon, and finally the specific antibodies.
Immunotherapy-induced pneumonitis – case report
Elena Jianu, Mădălin Tetu, Vlad Alexe, Teodor Horvat
Department of Thoracic Surgery, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
The incidence of immunotherapy-induced pneumonitis in literature ranged from 2.7% to 5%. The incidence increases when immunotherapies are combined. The risk factors that predispose patients to developing pneumonitis after immunotherapy are not known. We present the case of a 67-year-old man, former smoker (he stopped 7 years ago), with NSLC T3N2M1a stage IV, who underwent immunotherapy (line-two immunotherapy with nivolumab from July 2018 until December 2018). The patient presented with dyspnea at light efforts, and respiratory insufficiency with need of oxygen therapy. Chest computed tomography showed increase of ground glass infiltrate, suggesting acute interstitial pneumonitis pattern. Corticosteroid therapy was introduced with prednisone 1 mg/kg/bw and antibiotic therapy. An important clinical improvement was seen and the resolution of findings from controlled computed tomography. This disease diagnosis is difficult because of the variability of clinical and radiological presentation. The early diagnosis of pneumonitis in patients undergoing immunotherapy treatment is extremely important because of the great morbidity and mortality of this complication.
Posters
The expression of ERBB-2 and P53 proteins in the head and neck tumor
primary cell cultures
Marinela Bostan1, Georgiana Gabriela Petrică-Matei2, Gabriela Ion1, Viviana Roman1, Nicoleta Radu3, Mirela Mihăilă1,
Răzvan Hainăroşie4, Lorelei Irina Braşoveanu1
1. Center of Immunology, “Ştefan S. Nicolau” Institute of Virology, Bucharest
2. Personal Genetics, Medical Genetics Center, Department of Cytogenetics, Bucharest
3. Biotechnology Department & National Institute for Chemistry and Petrochemistry R&D of Bucharest, University of Agronomic Sciences and Veterinary Medicine of Bucharest
4. “Prof. Dr. Dorin Hociotă” Institute of Phonoaudiology and Functional ENT Surgery, Bucharest
The p53 tumor suppressor and the epidermal growth factor receptor (EGFR) play an essential role in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). EGFR is a tyrosine kinase receptor member of the ErbB receptor family and its aberrant activation leads to enhanced proliferation. In our study, we examined the expression of ERBB-2 and p53 proteins in HNSCC cells and their relevance for prognosis. Tumor specimens from non-treated patients having HNSCC were analyzed for ERBB-2 and p53 expression using ELISA and immunofluorescence assays. Nine specimens of HNSCC were successfully cultured out of a total number of 25 samples (36%). The majority of specimens that did not grow were taken from necrotic and infected tumors. We found p53 protein expressed in more than 10% of the cultured tumor samples. The analyses of the ERBB2 expression showed that 75% of tumor cell specimens were ERBB2-negative and 25% had a weak staining of ERBB2. The positive samples were obtained from patients having a good histological differentiation, lymphatic invasion and metastasis. We obtained a good correlation between the immunofluorescence and ELISA data. In conclusion, the results reveal the possibility to analyze more precisely the changes induced by various drugs in the expression of p53 or ERBB2.
Histone acetyltransferases in cervical oncogenesis
Anca Botezatu1, Adriana Pleşa1, Iulia V. Iancu1, Alina Fudulu1, Adrian Albulescu1, Irina Huica1, Demetra Socolov2, Gabriela Anton1
1. “Ştefan S. Nicolau” Institute of Virology, Bucharest
2. “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi
The mechanism by which human papillomavirus (HPV) induces tumorigenesis is based on the interaction of viral oncogenes E6 and E7 with different host cell regulatory molecules. Lately, it has been shown that histone acetyltransferases (HATs), which play an important role in the remodeling of chromatin, are also involved in various cancer types. This study aims to evaluate the acetylome in HPV-induced cervical neoplasia and the role of E7 oncogene on these chromatin modulators enzymes. Microarray was used to establish the gene expression profile in HeLa cell culture transfected with E7-siRNA. HATs belonging to GNAT and MYST familes were found among RNA species differentially expressed in transfected cells versus controls. The expression profile of these HATs was further quantified by qRT-PCR in RNA samples isolated from HPV positive and negative cervical biopsies harvested from women with cervical intraepithelial neoplasia (CIN1-CIN3) and squamous cervical carcinoma (SCC). HPV-DNA detection and genotyping were performed with commercially Linear Array HPV Genotyping Test (Roche Molecular Biochemicals), and E7 hrHPV (high-risk human papillomaviruses) levels were quantified by qRT-PCR using specific primers. As control, cervical swabs from women with negative tests for HPV-DNA and normal cytology were used. We found that HATs expression levels correlated with E7 HPV levels. From these chromatin modulators, p300 levels correlated significantly with E7 HPV expression. Low levels of KAT6B and p300 were found in patients versus control, the lowest being noted in SCC samples. Among HATs, KAT6B significantly correlated with hrHPV positivity, clinical parameters and metastasis (p<0.05). Conclusions. The results obtained highlight the role of histone acetyltransferases in cervical oncogenesis. P300 and KAT6B seems to be the epigenetic modulators whose expression correlates better with E7 HPV levels and the severity of the lesion.
Study supported by PNII RU-TE-2014-4-2502, Romanian Academy project and POS CCE ID 929, SMIS-CSNR 14049.
Experimental models in melanoma
Alexandra Budirinca, Maria Iuliana Gruia, Valentina Negoiţă, Rodica Anghel
“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Creating experimental models gives the possibility to assay new drugs’ potentials or combined therapy. The early detection of malignancy can be also studied in these in vivo models, and identifying the mechanisms represents a purpose for the research on the experimental models. In this study, we tried to get the morphological features of an experimental melanoma, in order to create new and efficient treatment protocols. To create experimental tumors, we used cells in culture donated by the Institute of Biochemistry. There were more types of melanic cells: reference cell lines B16, F1, F10, and transformed cell lines C and D, obtained after transfection with an angiogenic factor GCF2. These cells were inoculated in the right flank of the inbred C57B1/6 mice. Tumors appeared with a latency of 25 days, having an exponential growth after this period. The macroscopic features show an intense pigmentation of these tumors, which are well encapsulated, with a flaccid consistency; the tumor growth is very invasive locally and infiltrative in the underlying abdominal muscles. The metastasis appeared at different intervals, between 17 and 49 days, depending on the passages, the latency being longer as there were more passages. That means losing of the aggressiveness by serial grafts. Our partial results show the appearance of the melanoma at an approximate period of time for every cell line, without differences between in vivo and in vitro. Definitely, there are some adaptive and immunological mechanisms which cannot be quantified in cell lines, but must be taken into account in animal experiments.
Role of radiomic signature in predicting the response to neoadjuvant treatment
for locally advanced rectal neoplasm
Călin Gh. Buzea1, C.C. Mireştean1, Roxana Irina Iancu1,2, D.T. Iancu1,2
1. Regional Institute of Oncology, Iaşi
2. “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi
Radiomic is a noninvasive method to extract and analyze the undetectable characteristics through a visual analysis by the specialist physician using MRI/CT/PET-CT images, and to select those characteristics with prognostic or predictive value in the disease evolution and treatment. In case of locally advanced rectal cancer, the tumor regression grade (TRG) assessed by DWORAK score is a good predictor of the response to neoadjuvant treatment and even of disease-free survival (DFS). At present, applying the therapeutic standard represented by neoadjuvant chemo-radiotherapeutic multimodal treatment, only 20% of the patients will present, after the total mesorectal excision, complete tumoral resection, while 20-40% of the patients will have no regression or progressive disease revealed by the anatomopathological resected piece. The radiomic analysis in the oncological diagnosis and treatment is based on the analysis of shape, texture, and variations of grey levels or color immunogenicity. The radiomic signature can be an imaging biomarker useful in identifying those patients who will have a favorable response to a therapy, with the purpose of reducing the treatment and the number of “bad responders” for which the standard therapy proves suboptimal. The radiomic analysis can also identify patients with unfavorable evolutionary potential (metastatic disease or towards locoregional recurrence). The aim of this presentation is to highlight the possibility of a revolutionary non-invasive imaging method to predict the response to neoadjuvant therapy for non-metastatic locally advanced rectal cancer. The identification of predictive biomarkers can lead to the de-escalation of treatment in patients who will have a complete pathological response regarding regression (ypT0N0M0) and to escalation of treatment in patients who will progress or present the lack of regression after chemo-radiotherapy. Using a non-invasive biomarker, timely accesible and with reduced costs, can lead to the improvement and stratification of treatment in the multimodal treatment of locally advanced rectal cancer, within the concept of precision medicine.
The possibility of transforming the persistent immune reaction, induced by some parasitic zoonoses, in malignant lymphoma
Ana-Maria Coman1, Dragoş-Constantin Coman2, Nicolae Manolescu3
1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
2. The Sanitary-Veterinary and Food Safety Department, Prahova
3. The Romanian Academy
It is well known that the immune cell system has an overwhelming involvement in pathology, therefore, in the case of persistent stimulation, over a long period of time, it may take an unfavorable turn on the affected organism, its cellularity being marked by major changes, from blast cells multiplication to cellular atypias and monstrosities, thus prefiguring the worst malady of our century, cancer. Starting from this observation, we have investigated the lymph adenopaties from the slaughtered animals of sheep, swine and bovine species, who presented chronic parasitic infestations with Fasciola hepatica (sheep) or Echinococcus granulossus (swine and bovine). The cytomorphological screening allowed us to individualize the entire “lesion movie pictures” of the transformations from chronic lymphadenitis to malignant pre-lymphoma that could be correlated with the continuous stimulated of the lymph node by the hyperantigenicity induced by chronic parasitism.
Advantages of using transplantable ascitic tumors in experimental oncology
Maria Alexandra Dumitru, Ana Maria Coman
“Prof. Dr. Alex. Trestioreanu” Institute of Oncology, Bucharest
The complexity of the issues raised by the prophylaxis, detection, diagnosis and treatment of cancer brings a better understanding of how this disease develops and how it can be combated as efficiently as possible. Thus, the clinician, human doctor or veterinarian, cannot ignore the basics of the fundamental biology of cancer. In the present study, the authors want to highlight the importance and benefits of using experimental models, particularly tumor-ascitic forms, in biological cancer studies, as well as the appropriate techniques of ascitic conversion of various tumor lines maintained on different hosts.
EGFR status and cellular proliferation in urinary bladder cancer – POSTER
Mirela Dumitru1, Monica Graţiela Horţopan2, Monica Maria Vasilescu1, Mirela Mihailat3, Camelia Mia Hotnog3,
Lorelei Irina Braşoveanu3, Marieta Elena Panait1, Maria Iuliana Gruia1
1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
2. Fundeni Clinical Hospital, Bucharest
3. “Ştefan S. Nicolau” Institute of Virology, Bucharest
One purpose for the quantification of EGFR status in patients with urinary bladder cancer is to identify high-risk features that might direct target therapy. EGFR plays an important role in carcinogenesis, cell survival, cell apoptosis, tumor metastasis, and angiogenesis via activating the EGFR signaling network. EGFR and HER2 proteins are the primary signal proteins involved in the pathway of signal transduction cascade in tumor proliferation. It has been reported that the expression of EGFR and HER2 promotes cell migration, which plays an important role in cellular metastasis. Since EGFR/HER2 receptors heterodimerization are evident in vitro, the implication of coexpression patterns in bladder cancer in the clinical setting needs further clarifications. We evaluated the expression of EGFR and HER2 in tumors of urinary bladder to determine the correlation between gene expression and tumor proliferation potential. Human bladder cancer tissues were analyzed by immunohistochemistry for EGFR and HER2 expression and by chromogenic in situ hybridization for EGFR gene amplification. DNA content from single tumor cell suspension was investigated by flow cytometry for DNA ploidy level and S-phase fraction. We observed EGFR overexpression in 48% of samples and EGFR gene amplification in 41% of EGFR-positive cases. EGFR and HER2 co-expression in urinary bladder carcinomas was associated with lymph node metastases, aneuploidy and a high S-phase fraction. The EGFR expression was higher in non-diploid tumors compared with diploid carcinomas. Given the molecular heterogeneity of urinary bladder cancer, the determination of EGFR status could contribute to the identification of the patients with an aggressive biological behavior. Targeting more than one surface receptor could allow for more efficient tumor cell death across metastatic and invasive bladder carcinomas.
Study on the role of proteinases during the development of Walker-256 carcinosarcoma in vivo and in vitro
Daniela Glavăn1, Maria Iuliana Gruia1, Valentina Negoiţă1, Camelia Mia Hotnog2, Mirela Mihăilă2, Lorelei Irina Braşoveanu2
1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
2. Center of Immunology, “Ştefan S. Nicolau” Institute of Virology, Bucharest
Metastasis is one of the most important steps in the cancer evolution because it is responsible for most cancer mortality. That is way it is absolutely necessary to find new therapeutic targets and new tumor biomarkers which would help in the early detection of metastases and prognosis. Tumor cells produce and release a lot of proteolytic enzymes and these proteases may be important in the progression of several human tumors. MMP-2 (gelatinase A) is a zinc-endopeptidase which plays an important role in tumor invasion and metastasis. This enzyme is present in nearly all human cancers and can influence the tumor environment by promoting angiogenesis, tumor growth and metastasis. Cathepsin D is a lysosomal endopeptidase which facilitates extracelllar matrix degradation, an important stage in tumoral invasion. A strong predictive value was found for cathepsin D concentration in breast cancer, as well as in many types of tumors. An investigation of serum MMP-2 and cathepsin D levels, in rats bearing Walker-256 carcinosarcoma and in LLC-WRC 256 cell line treated with epirubicin, cyclophosphamide and some flavonoids like quercetin, resveratrol and curcumin, versus untreated cells, reported a positive correlation between the concentrations of these two biomarkers and disease evolutions. The analysis of the data obtained with the modulation of MMP-2 release in the LLC-WRC 256 cell line treated with cytostatics and biocompatients demonstrated that the 24-hour treatment with all three biochemicals studied reduced the levels of this proteinase, the same effect being significant in the treatments with cytostatics at 48 hours and at 72 hours. Combined cytostatic drugs prolonged at 72 hours causes decrease of cathepsin D levels. Sequential cytostatic treatment followed by RSV determines a decrease in cathepsin D levels over 48 and 72 hours versus RSV prior to cytostatics. The modulation of the protein expression of biomarkers, as well as their functional role in angiogenesis, proliferation and metastasis could be beneficial in selecting potential targets useful in synthesizing new drugs with a role in personalized, accurate medicine.
The measurement of some molecular effects induced after experimental tumors treatment with 177-Lu-Neurotensin
Maria Iuliana Gruia1, Diana Chiper2, Valentina Negoiţă1, Dana Nicolae2, Valeria Lungu2, Marieta Panait1
1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
2. National Institute of Physics and Nuclear Engineering, Bucharest
Somatostatin-derived drugs are now widely used for tumor therapy and diagnosis. Other regulatory peptides are now candidate as tumor-targeting agents, and an increasing number of tumors may be addressed by “peptide-bullet” strategy: peptide can be conjugated with cytotoxic moieties or radionuclides and, provided the receptor-ligand complex is internalized on binding, the functional moiety can be specifically delivered into the tumor cell. Neurotensin is a 13-aminoacid regulatory peptide and has already been studied as a candidate for peptide receptor targeting. Like other neuropeptides, neurotensin has different functions. It is a neurotransmitter and neuromodulator in the central nervous system and a local paracrine hormone in the periphery, particularly in the gastrointestinal tract. Neurotensin may act in an endocrine fashion to affect tumor growth. Acting through the neurotensin receptors, neurotensin is known to stimulate various signal transduction pathways, including intracellular calcium Ca2+, the mitogen activated protein kinases (MAPK), ERKand JNK, and various PKC isoforms. Reactive oxygen species (ROS) are thought to be involved in the pathogenesis of many different types of cancers. ROS play a role in processes that promote cell growth and regulate other biologic functions such as gene expression or migration of cells. It has been demonstrated that increased production of ROS can lead to a transforming phenotype. ROS are also formed in normal cells in response to a variety of stimuli. The aim of our paper is to identify some biological effects manifested at molecular level in experimental animals after the treatment with 177-Lu-NT.
Modulation of cell adhesion profile associated to colon cancer cell lines by bioactive compounds
Camelia Mia Hotnog, Mirela Mihăilă, Marinela Bostan, Lorelei Irina Braşoveanu
Center of Immunology, “Ştefan S. Nicolau” Institute of Virology, Bucharest
Cell adhesion represents a main component of cell migration and recognition processes, which are involved in proliferation, differentiation, apoptosis, and immune and inflammatory responses. Cancer initiation, invasion and tumor progression are closely associated with a decreased dependence on cell adhesion, needed for growth and survival. Biomarkers like ICAM-1, EpCAM or E-cadherin are considered potential immunotherapeutic targets because they play an important role in releasing cells from the primary tumors and invasion of tumor cells in other tissues. Targeted molecular therapy involves a growing number of agents that can interfere with the intrinsic mechanisms of tumor cells and have the advantage of a lower toxicity than classical anticancer drugs. Therefore, our study focused on the possible modulation of molecules from a cell adhesion panel by cytotoxic drugs (5-fluorouracil, 25 mM) or bioactive compounds (curcumin, 50 mM), associated to colon cancer cell lines (LoVo, wild-type p53 and HT-29, mutated p53 cells). After 24 hours, adherent cultured cells were detached from the culture flasks, lysed and the total lysate protein quantified. 100 mg of total protein from every culture treatment and non-treated cells were used in further determinations. The relative protein expression of the 17 biomolecules included in the panel was evaluated by protein microarray technique, using RayBio® Human Adhesion Antibody Array G-Series 1 kit and GenePix Pro 7 fluorescence scanner. The obtained results showed a differential constitutive expression of cell adhesion molecules in the two cell lines and the modulatory action of biocompounds on the protein expression in treated versus untreated colon cells.
The detection of oxidative stress in the dinamics of the surgical treatment
Şerban Marinescu, Oana Trifănescu, Bogdan Filimon, Maria Iuliana Gruia
“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Oxidative stress can be defined as a dynamic imbalance caused by the production of a strong flow of active oxygen metabolites at the expense of endogenous antioxidant protection systems. This study aims to determine some biochemical parameters of oxidative stress in the dynamics of the surgical treatment. We studied a group of patients with breast, cervical and ovarian cancer in the dynamics of the operative act, more exactly before surgery, at 24 hours and 7 days after surgery. The results demonstrate that the tumor is an oxidative stress factor and that the operative act does not induce oxidative stress. The findings of this study refer to the need to monitor the redox balance in oncological patients, with oxidative stress being required in some vital or destructive signaling systems, following oncological treatments.
Reversing resistance to chemo- and immunotherapy in T47D breast cancer cell line
Mirela Mihăilă, Camelia Hotnog, Marinela Bostan, Viviana Roman, Ion Gabriela, Lorelei I. Braşoveanu
Center of Immunology, “Ştefan S. Nicolau” Institute of Virology, Bucharest
Breast cancers are malignancies with high incidence and mortality throughout women, their etiology involving many genetic, immunological and biochemical factors. The main obstacle against the success of therapy in many cancers seems to be the impossibility of eradication of all tumor cells. Thus, the need for effective, lasting breast cancer treatment is urgent. Depending on the stage and molecular characteristics of the cancer when diagnosed, breast cancer surgery may be followed by additional chemotherapy, radiation, or targeted therapies, including hormone therapy and immunotherapy with targeted antibodies, such as trastuzumab (Herceptin®). Effects of mAb treatments might be impared by complement regulatory molecules (CRM), like protectin. Therefore, our study focused on the investigation of levels of expression of several tumor-associated antigens (TAA) as potential targets for cancer immunotherapy, and breast-associated CRM, followed by modulation experiments of their expression by cytokines or bioactive compounds. Antigen expression was evaluated by indirect immunofluorescence, followed by acquisition and analysis by flow-cytometry. In addition, functional roles of molecules under study were examined in complement and cell-mediated cytotoxicity assays, performed by real-time cell analysis (RTCA) using xCELLigence technology. Our results indicated a higher sensibility of breast cancer cells to lysis when combined treatments were used. New therapeutic strategies for breast cancer are needed to improve clinical outcomes for breast cancer patients, particularly in those with advanced disease.
IMRT/VMAT comparative dosimetric assessment for structures involved
in oral radiomucositis in locally advanced oropharyngeal neoplasms treated
with radio-chemotherapy
C.C. Mireştean1, Cătalina Teacă1, Luminiţa Gurguţă1, Călin Gh. Buzea1, Roxana Irina Iancu1,2, D.T. Iancu1,2
1. Regional Institute of Oncology, Iaşi
2. “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi
Radiotherapy is an essential part of the multidisciplinary management of head and neck cancers. Although the locoregional control is one of the main goals, it is difficult to obtain a high therapeutic report with an increased rate of efficacity/toxicity index. IMRT technique proved to be non-inferior to 3D-CRT radiotherapy in the irradiation on locally advanced head and neck cancers regarding locoregional control, and to be superior in protecting radiosensible organs, especially the parotid glands. Volumetric arc therapy with modulated intensity (VMAT) proved simillar effectiveness as IMRT in framing the targeted volumes and protecting the radiosensible organs, with a possible radiobiological benefit of reducing the treatment period and the high-dose rate. The aim of the study is to assess the doses received by oral cavity through VMAT technique in relation to the doses received using the IMRT technique in a number of 40 cases of non-metastatic locally advenced oropharyngeal cancers treated multimodally with chemotherapy and radiotherapy. The assessment of the rapport between the doses received by parotid and by oral cavity could be at the basis of conceiving a predictive model of oral mucositis beginning from the premise that the decrease of salivary volume and of the biochemical quality of saliva is an aggravating factor of mucositis. In case of the undelimitation of oral cavity as OAR, the maximum doses received by VMAT technique are above 35 Gy in most cases, and when the dose cannot be limited to at least one parotid gland (<26 Gy), xerostomia can aggravate oral mucositis. Using the VMAT technique, the parotid glands receive similar doses to those from the IMRT technique, but oral cavity is more exposed to toxicity. The delimitation of oral cavity as OAR and applying the dosimetric constraints are necessary in VMAT irradiation of oropharyngeal cancers.
Effects of Zingiber officinale extract in melanoma
Cristina Niţu2, Diana Costin1, Iuliana Gruia2, Cristina Munteanu1, Marieta Costache1, Anca Dinischiotu1, Gheorghe Stoian1
1. Multi User Research Center in Molecular Biology (MURC-MB), University of Bucharest
2. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
Zingiber officinale has been widely studied for its pharmacological activities and it has been reported to exhibit anti-inflammatory, antipyretic, antimicrobial, hypoglycemic, antimigraine, antischistosomal, antioxidant, hepatoprotective, diuretic, hypocholesterolemic and antihypertensive activities. Recent studies show that ginger extract exibits a variety of biological activities, among them being the antitumoral one. The mechanisms involved in the antitumour effects involve a multitude of interdependent processes, such as gene expression, cell signalling, the induction or inhibition of different enzymatic activities, some of them incompletely studied. The aim of our study was to investigate the anti-proliferative and antitumoral role of fresh ginger extract on C32 melanoma cell line by analyzing three enzymes implicated in the cell redox process, SOD, GR and GST, matrix metalloproteinases and LDH from culture medium. Research data show that malign process is caused, among other things, by derivatives of citotoxic oxygen or by hydroxil radicals, compounds which under normal circumstances are initially detoxified by the antioxidant enzymatic system. For this reason we decided to study the variation of the specific activity of the enzymes and to monitor their modification due to the treatment of tumoral cells with fresh ginger extract.
Expression of topoisomerases as indicator of MCF-7 cells response to adriablastin treatment
Maria Monica Vasilescu1, Maria Iuliana Gruia1, Camelia Hotnog2, Mirela Mihăilă2, Marinela Bostan2, Marieta Elena Panait1,
Lorelei Irina Braşoveanu2
1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest
2. Center of Immunology, “Ştefan S. Nicolau” Institute of Virology, Bucharest
Topoisomerases have been shown to be primary cellular targets for a number of chemotherapeutic agents commonly used to treat many types of cancer. Knowing the status of these enzymes in a tumor shows therefore the special importance for the response to chemotherapy. The aim of the present study was to evaluate the expression of topoisomerase I (Topo I), alpha and beta isoforms of topoisomerase II (Topo IIa and Topo IIb) by flow cytometry and Western Blot and the response to adriablastin in the cells of the human breast cancer line MCF-7 and adriablastin-resistant subline MCF-7/AR obtained by continuous exposure to increasing concentrations of cytostatic, using MTS technique and flow cytometry for cell viability determination. The data obtained showed that Topo IIa expression was associated with the cells response to ADB treatment, so its increased expression in MCF-7 cells was associated with increased sensitivity to ADB, while the low expression determined in MCF-7/AR cells was associated with a lower response rate. The existence of a different susceptibility pattern of topoisomerases to chemotherapeutic agents may constitute an important parameter to be evaluated in studies with topoisomerases inhibitors.